Histoplasmosis Complicating Tumor Necrosis Factor-α Blocker Therapy

A Retrospective Analysis of 98 Cases

Paschalis Vergidis, Robin K. Avery, L. Joseph Wheat, Jennifer L. Dotson, Maha A. Assi, Smyrna A. Antoun, Kassem A. Hamoud, Steven D. Burdette, Alison G. Freifeld, David S. McKinsey, Mary E. Money, Thein Myint, David R. Andes, Cynthia A. Hoey, Daniel A. Kaul, Jana K. Dickter, David E. Liebers, Rachel A. Miller, William E. Muth, Vidhya Prakash & 3 others Frederick T. Steiner, Randall C. Walker, Chadi Hage

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background. Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Original languageEnglish (US)
Pages (from-to)409-417
Number of pages9
JournalClinical Infectious Diseases
Volume61
Issue number3
DOIs
StatePublished - Aug 1 2015

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Histoplasmosis
Tumor Necrosis Factor-alpha
Therapeutics
Odds Ratio
Confidence Intervals
Histoplasma
Recurrence
Azoles
Biological Factors
Amphotericin B
Disease Management
Immunosuppression
Adrenal Cortex Hormones
Logistic Models
Urine

Keywords

  • adalimumab
  • etanercept
  • histoplasmosis
  • immune reconstitution syndrome
  • infliximab

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Histoplasmosis Complicating Tumor Necrosis Factor-α Blocker Therapy : A Retrospective Analysis of 98 Cases. / Vergidis, Paschalis; Avery, Robin K.; Wheat, L. Joseph; Dotson, Jennifer L.; Assi, Maha A.; Antoun, Smyrna A.; Hamoud, Kassem A.; Burdette, Steven D.; Freifeld, Alison G.; McKinsey, David S.; Money, Mary E.; Myint, Thein; Andes, David R.; Hoey, Cynthia A.; Kaul, Daniel A.; Dickter, Jana K.; Liebers, David E.; Miller, Rachel A.; Muth, William E.; Prakash, Vidhya; Steiner, Frederick T.; Walker, Randall C.; Hage, Chadi.

In: Clinical Infectious Diseases, Vol. 61, No. 3, 01.08.2015, p. 409-417.

Research output: Contribution to journalArticle

Vergidis, P, Avery, RK, Wheat, LJ, Dotson, JL, Assi, MA, Antoun, SA, Hamoud, KA, Burdette, SD, Freifeld, AG, McKinsey, DS, Money, ME, Myint, T, Andes, DR, Hoey, CA, Kaul, DA, Dickter, JK, Liebers, DE, Miller, RA, Muth, WE, Prakash, V, Steiner, FT, Walker, RC & Hage, C 2015, 'Histoplasmosis Complicating Tumor Necrosis Factor-α Blocker Therapy: A Retrospective Analysis of 98 Cases', Clinical Infectious Diseases, vol. 61, no. 3, pp. 409-417. https://doi.org/10.1093/cid/civ299
Vergidis, Paschalis ; Avery, Robin K. ; Wheat, L. Joseph ; Dotson, Jennifer L. ; Assi, Maha A. ; Antoun, Smyrna A. ; Hamoud, Kassem A. ; Burdette, Steven D. ; Freifeld, Alison G. ; McKinsey, David S. ; Money, Mary E. ; Myint, Thein ; Andes, David R. ; Hoey, Cynthia A. ; Kaul, Daniel A. ; Dickter, Jana K. ; Liebers, David E. ; Miller, Rachel A. ; Muth, William E. ; Prakash, Vidhya ; Steiner, Frederick T. ; Walker, Randall C. ; Hage, Chadi. / Histoplasmosis Complicating Tumor Necrosis Factor-α Blocker Therapy : A Retrospective Analysis of 98 Cases. In: Clinical Infectious Diseases. 2015 ; Vol. 61, No. 3. pp. 409-417.
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abstract = "Background. Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3{\%}). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95{\%} confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95{\%} CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4{\%}) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9{\%}) patients and later resumed in 25 of 74 (33.8{\%}) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2{\%} at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2{\%}. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.",
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T1 - Histoplasmosis Complicating Tumor Necrosis Factor-α Blocker Therapy

T2 - A Retrospective Analysis of 98 Cases

AU - Vergidis, Paschalis

AU - Avery, Robin K.

AU - Wheat, L. Joseph

AU - Dotson, Jennifer L.

AU - Assi, Maha A.

AU - Antoun, Smyrna A.

AU - Hamoud, Kassem A.

AU - Burdette, Steven D.

AU - Freifeld, Alison G.

AU - McKinsey, David S.

AU - Money, Mary E.

AU - Myint, Thein

AU - Andes, David R.

AU - Hoey, Cynthia A.

AU - Kaul, Daniel A.

AU - Dickter, Jana K.

AU - Liebers, David E.

AU - Miller, Rachel A.

AU - Muth, William E.

AU - Prakash, Vidhya

AU - Steiner, Frederick T.

AU - Walker, Randall C.

AU - Hage, Chadi

PY - 2015/8/1

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N2 - Background. Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

AB - Background. Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

KW - adalimumab

KW - etanercept

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KW - immune reconstitution syndrome

KW - infliximab

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